This grant application is a continuation of a longitudinal study of aging and Alzheimer's disease in a defined population of 678 Catholic sisters who were 75 to 102 years old when the study began in 1991. By the end of 2001, approximately 250 survivors will range in age from 85 to as old as 107 years. The continuation of the Nun Study will provide valuable data on the oldest old (85+), the fastest growing segment of the American population. Early and late life risk factors documented in convent archives, annual assessments of cognitive and physical function, and brain donation by all participants make the Nun Study a unique resource. Because of the high level of homogeneity of adult lifestyles, many factors that confound other epidemiologic studies will be eliminated or minimized, such as smoking, occupation, reproductive history, and access to health care. More than ten years of extensive data collection provide us with the opportunity to describe the natural history of cognitive dysfunction from intact cognitive status, to mild cognitive impairment, to early and late stages of dementia. At the other extreme, our data allow us to investigate the determinants of survival and successful aging in the very old. Our study also is enhanced by combining the gross and microscopic findings from autopsies with data from postmortem MR images. Aim I. Mild cognitive impairment: Identify risk factors for both the development of mild cognitive impairment and its conversion to dementia. Determine if the risk factors for the development of mild cognitive impairment are different from those for the conversion to dementia. Aim II. Alzheimer's disease and dementia: Determine why some individuals with relatively little neuropathology succumb to the clinical manifestations of dementia, while others with severe neuropathology do not develop dementia. Furthermore, describe how this difference in the clinical expression of neuropathology is due in part to early life factors as well as increasing age. Aim Ill. Successful aging and longevity: Describe the relationship of Alzheimer's and cerebrovascular pathology to successful aging and longevity, and the role early life factors play in this relationship.